crossing96/oncoscreening huggingface dataset:
XRCC1 polymorphisms associated with survival among Chinese bladder cancer patients receiving epirubicin and mitomycin C.	The association between DNA repair gene polymorphisms and bladder cancer risk has been widely studied. However, only few studies have examined the correlation between bladder cancer and instillation agent sensitivity. The aim of this study was to examine the association between polymorphisms of DNA repair genes, namely X-ray repair cross-complementing group I (XRCC1) rs2854509 and rs3213255, and bladder cancer recurrence risk. We recruited 244 patients (130 treated with epirubicin and 114 treated with mitomycin C). Genomic DNA was used to examine the XRCC1 rs2854509 and rs3213255 genotypes by Taqman PCR analysis. Combination analysis of XRCC1 rs2854509 and rs3213255 and examination of XRCC1 diplotypes were performed to reveal possible correlations. The rs2854509 CC and rs3213255 TT genotypes conferred shorter survival times than the rs2854509 AC/AA and rs3213255 CC/CT genotypes in patients treated with epirubicin, but not in those treated with mitomycin C (MMC) in adjusted models [hazard ratio (HR) = 0.23, 95 % confidence interval (CI) = 0.10-0.53 for rs2854509 AC + AA compared with CC; HR = 0.17, 95 % CI = 0.06-0.46 for rs3213255 CC + CT compared with TT]. Combination analysis showed significantly increased recurrence-free survival (RFS) among patients simultaneously carrying the rs2854509 AC/AA and rs3213255 CC/CT genotypes with an HR of 0.15 (95 % CI = 0.05-0.45) compared to those carrying other genotypes. Diplotype analysis demonstrated that the A-C/C-T diplotype is associated with a lower risk of recurrence compared with the common wild C-T/C-T diplotype (HR = 0.17, 95 % CI = 0.06-0.51). Our results suggest that the rs2854509 CC and rs3213255 TT genotypes confer higher sensitivity to epirubicin instillation. Moreover, the A-C/C-T diplotype presents significantly lower recurrence risk than other diplotypes.	bladder
Bladder cancer mortality after spinal cord injury over 4 decades.	PURPOSE: We estimate bladder cancer mortality in people with spinal cord injury compared to the general population. MATERIALS AND METHODS: Data and statistics were retrieved from the National Spinal Cord Injury Statistical Center and the National Center for Health Statistics. The mortality experience of the 45,486 patients with traumatic spinal cord injury treated at a Spinal Cord Injury Model System or Shriners Hospital was compared to the general population using a standardized mortality ratio. The standardized mortality ratio data were further stratified by age, gender, race, time since injury and injury severity. RESULTS: Our study included 566,532 person-years of followup between 1960 and 2009, identified 10,575 deaths and categorized 99 deaths from bladder cancer. The expected number of deaths from bladder cancer would have been 14.8 if patients with spinal cord injury had the same bladder cancer mortality as the general population. Thus, the standardized mortality ratio is 6.7 (95% CI 5.4-8.1). Increased mortality risk from bladder cancer was observed for various ages, races and genders, as well as for those injured for 10 or more years and with motor complete injuries. Bladder cancer mortality was not significantly increased for ventilator users, those with motor incomplete injuries or those injured less than 10 years. CONCLUSIONS: Individuals with a spinal cord injury can potentially live healthier and longer by reducing the incidence and mortality of bladder cancer. Study findings highlight the need to identify at risk groups and contributing factors for bladder cancer death, leading to the development of prevention, screening and management strategies.	bladder
Food and Drug Administration process for development and approval of drugs and radiopharmaceuticals: treatments in urologic oncology.	Regulatory advice and assessment play an important role in the successful development of new drugs and radiopharmaceuticals for the treatment of urologic malignancies. Cooperation between the US Food and Drug Administration (FDA) and the pharmaceutical industry has led to the approval of more than 20 new urologic oncology products in the last 2 decades. Despite these advances, more effective treatments need to be developed and approved for the treatment of urologic malignancies. This review provides general information about the FDA's role in the development of investigational new drugs, with an emphasis on the regulatory process and the requirements for marketing approval. In addition, this review summarizes the products for the treatment of urologic malignancies that were approved by the FDA in the last 30 years and the key issues concerning urologic oncology products that were discussed publicly at Oncologic Drug Advisory Committee meetings in the past 10 years.	bladder
Mortality among chemical plant workers exposed to acrylonitrile: 2011 follow-up.	OBJECTIVES: To update a cohort study of chemical workers and reevaluate lung cancer mortality in relation to acrylonitrile (AN) exposure. METHODS: Subjects were 2096 workers employed during 1955 to 2011. We identified 474 deaths through 2011, and quantitatively estimated worker exposures to AN. Analyses included national and county-based standardized mortality ratios and relative risk regression of internal cohort rates. RESULTS: We found no statistically significant excess mortality risks associated with Lima employment for any cause of death category, including lung cancer and other cancer sites implicated in previous studies. CONCLUSIONS: This update provides no evidence that exposure to AN at levels experienced by Lima workers is associated with an increased risk of lung cancer mortality, as suggested in original study. Earlier reported bladder cancer risks decreased to a much lower, not statistically significant level.	bladder
The association between NQO1 Pro187Ser polymorphism and urinary system cancer susceptibility: a meta-analysis of 22 studies.	Numerous studies have investigated the association between NQO1 Pro187Ser polymorphism and urinary system cancer risk, but the findings are inconsistent. To derive a more precise estimation of such association, we performed a meta-analysis based on 22 publications encompassing 5,274 cases and 6,459 controls. Overall, significant association was found between NQO1 Pro187Ser polymorphism and urinary system cancer risk. Moreover, stratified analysis observed a statistically significant association for bladder cancer, prostate cancer, renal cell carcinoma, Caucasians, Asians, and hospital-based studies. In summary, this meta-analysis indicated that NQO1 Pro187Ser polymorphism conferred genetic susceptibility to urinary system cancer.	bladder
[Cost-effectiveness of transurethral resection of the bladder with blue light in patients with non muscle invasive bladder cancer in France].	"OBJECTIVE: Photodynamic diagnosis after instillation of hexylaminolevulinate (Hexvix(®)) during transurethral resection of the bladder (TURB) helps in the detection of tumors and results in a reduction of recurrence. The medical and economic impact of fluorescence compared to conventional white light TURB needed to be analyzed in the French healthcare system. The aim of this study was to evaluate the medical and economic impact of the blue light TURB in the treatment of NMIBC. MATERIALS AND METHODS: A cost-utility model, based on data from the literature and expert opinions, combining a decision tree and a Markov model was used to simulate the initial management after a first TURB of all new patients diagnosed with symptoms consistent with NMIBC and outcomes at short and long terms. In this model, the initial TURB could be achieved either with fluorescence in addition to white light, or with white light only. The main criteria of the model was based on the quality adjusted life years (QALY). The economic evaluation focused on the direct costs. The test's results and costs were determined from diagnosis until death of patients. RESULTS: The use of photodynamic diagnosis during TURB resulted in an improvement in QALYs (0.075) and a reduction of € 670 of the costs compared to the conventional treatment with white light. Thus, the blue light resection was defined as a strategy called ""dominant"" over the TURB in white light. CONCLUSION: In the context of the French health system, the model of the study showed that the blue light cystoscopy during TURB was associated with increased QALYs and reduced health spending. This kind of result is rare in oncology. This health economic analysis confirms the interest of hexylaminolevulinate acid in initial management of NMIBC, according to studies conducted in United Kingdom, Italy and Poland."	bladder
Management of advanced bladder cancer in the era of targeted therapies.	Systemic chemotherapy is the standard treatment of advanced and metastatic urothelial carcinoma of the bladder (UCB). Unfortunately, systemic chemotherapy is ineffective in a significant number of patients, while side effects occur frequently. Detailed molecular-genetic investigations revealed a broad heterogeneity of underlying genomic mutations in UCB and led to the detection of cancer-specific therapeutic targets. These findings may allow a more tailored and individualized patient-based therapy, focusing on specific genomic variations, which may cause chemo-resistance in patients progressing or relapsing after standard chemotherapy. Targeted therapies hold the potential to be more effective in inhibiting cancer cell growth and progression, as well as to cause fewer side effects. While targeted therapies have been successfully established in the treatment of various malignancies including renal cell carcinoma, the clinical impact of these modern treatment strategies still remains unsettled for UCB. In this review, we comprehensively summarize the most current and relevant findings on targeted therapy in advanced and metastatic UCB, elucidating chances and limitations and discussing future perspectives.	bladder
Nitrate in drinking water and bladder cancer risk in Spain.	BACKGROUND: Nitrate is a widespread contaminant in drinking water and ingested nitrate under conditions resulting in endogenous nitrosation is suspected to be carcinogenic. However, the suggested association between nitrate in drinking water and bladder cancer remains inconsistent. We evaluated the long-term exposure to drinking water nitrate as a risk factor for bladder cancer, considering endogenous nitrosation modifiers and other covariables. METHODS: We conducted a hospital-based case-control study of bladder cancer in Spain (1998-2001). Residential histories and water consumption information were ascertained through personal interviews. Historical nitrate levels (1940-2000) were estimated in study municipalities based on monitoring records and water source. Residential histories of study subjects were linked with nitrate estimates by year and municipality to calculate individual exposure from age 18 to recruitment. We calculated odds ratios (OR) and 95% confidence intervals (CI) for bladder cancer among 531 cases and 556 controls with reliable interviews and nitrate exposure information covering at least 70% of years from age 18 to interview. RESULTS: Average residential levels ranged from 2.1mg/L to 12.0mg/L among regions. Adjusted OR (95%CI) for average residential levels relative to ≤ 5 mg/L were 1.2 (0.7-2.0) for >5-10mg/L and 1.1 (0.6-1.9) for >10mg/L. The OR for subjects with longest exposure duration (>20 years) to highest levels (>9.5mg/L) was 1.4 (0.9-2.3). Stratification by intake of vitamin C, vitamin E, meat, and gastric ulcer diagnosis did not modify these results. A non-significant negative association was found with waterborne ingested nitrate with an OR of 0.7 (0.4-1.0) for >8 vs. ≤ 4 mg/day. Adjustment for several covariables showed similar results to crude analyses. CONCLUSION: Bladder cancer risk was inconsistently associated with chronic exposure to drinking water nitrate at levels below the current regulatory limit. Elevated risk is suggested only among subjects with longest exposure duration to the highest levels. No evidence of interaction with endogenous nitrosation modifiers was observed.	bladder
Forkhead box protein P3 (Foxp3) expression serves as an early chronic inflammation marker of squamous cell differentiation and aggressive pathology of urothelial carcinomas in neurological patients.	OBJECTIVE: To establish whether the expression of forkhead box protein P3 (Foxp3) provides specific diagnostic information about neurological patients with urothelial carcinoma of the bladder (UCB). PATIENTS AND METHODS: UCB tissue samples from neurological patients were retrieved and compared with control samples. The expression of Foxp3 was analysed via immunohistochemistry of microarray tissue sections. The correlation between Foxp3 expression, histological parameters and tumour stage was assessed. RESULTS: Overall, 20 UCB tissue samples and 20 others without UCB from neurological patients, and 46 UCB tissue samples from non-neurological patients were analysed. The distribution of pT of UCB in the neurological patients was as follows: one low-grade pTa (5%), three high-grade pTa (15%), three pT1(15%), one pT2(5%), seven pT3(35%) and five pT4(25%). Squamous cell differentiation was seen in nine UCB samples (45%). Foxp3 expression was detected in tumour tissues, including one pTa high grade, one pT1, one pT2, five pT3 and five pT4 tumours. Foxp3 was expressed in 11/13 muscle-invasive tumours. All tumours displaying squamous cell differentiation expressed Foxp3. Foxp3 was not expressed in the pT3 tumours that displayed sarcomatoid and micropapillary properties. Among the bladder samples without UCB from neurological patients, no expression of Foxp3 was observed. Among the UCB samples from the non-neurological patients, only seven displayed squamous cell differentiation. All tumours that displayed squamous cell differentiation expressed Foxp3, including one pTa high grade, four pT3 and two pT4 tumours. Other tumours displaying urothelial differentiation did not express Foxp3. The expression of Foxp3 correlated to squamous cell differentiation in neurological (P = 0.004) and non-neurological UCB tissue (P < 0.001). In neurological, but not non-neurological UCB tissue, the expression of Foxp3 correlated with the muscle-invasive stage (P = 0.022). CONCLUSIONS: Elevated expression of Foxp3 appears to be a characteristic of neurological patients presenting with aggressive UCB and squamous cell differentiation. Targeting Foxp3 may represent a novel strategy to improve anti-tumour immunotherapy for UCB.	bladder
Effect of perioperative blood transfusion on mortality for major urologic malignancies.	INTRODUCTION: Patients who undergo surgical treatment for malignancy often receive perioperative blood transfusion (PBT). We examined the association between PBT and mortality in patients who received surgical treatment of prostate, bladder, and kidney cancer. MATERIALS AND METHODS: Using the Surveillance, Epidemiology, and End Results-Medicare data set from 1992-2009, we identified 28,854 men with prostate cancer, 5462 patients with bladder cancer, and 14,379 patients with renal cell carcinoma who underwent radical prostatectomy (RP), radical cystectomy (RC), or radical (RN) or partial nephrectomy (PN) as primary therapy. Univariate and multivariate models were used to evaluate the association of PBT with cancer-specific mortality (CSM) and all-cause mortality (ACM). RESULTS: The rate of PBT in bladder and kidney cancer have been increasing over time, and PBT in prostate cancer steadily increased and peaked in 2002 and declined afterward. The median follow-up for the RP, RC, and RN/PN cohorts were 70 months, 21 months, and 39 months, respectively. In the RP cohort, PBT was associated with greater CSM (hazard ratio [HR], 1.609; 95% confidence interval [CI], 1.235-2.097; P = .0004) and ACM (HR, 1.121; 95% CI, 1.006-1.251; P = .0394). In the RC cohort, PBT was not associated with greater CSM (HR, 1.047; 95% CI, 0.917-1.195; P = .4962) or ACM (HR, 1.095; 95% CI, 0.998-1.200; P = .0547). In the nephrectomy cohort, PBT was associated with greater CSM (HR, 1.365; 95% CI, 1.167-1.597; P = .0001) and ACM (HR, 1.402; 1.273-1.544; P < .0001). CONCLUSION: PBT was associated with increased CSM and ACM for prostate and kidney cancer in a multivariate model. Although these data do not identify a causative relationship between PBT and mortality, efforts made to limit PBT in patients who undergo urologic cancer surgery can yield long-term survival benefits.	bladder
The microbiome of the urinary tract--a role beyond infection.	Urologists rarely need to consider bacteria beyond their role in infectious disease. However, emerging evidence shows that the microorganisms inhabiting many sites of the body, including the urinary tract--which has long been assumed sterile in healthy individuals--might have a role in maintaining urinary health. Studies of the urinary microbiota have identified remarkable differences between healthy populations and those with urologic diseases. Microorganisms at sites distal to the kidney, bladder and urethra are likely to have a profound effect on urologic health, both positive and negative, owing to their metabolic output and other contributions. Connections between the gut microbiota and renal stone formation have already been discovered. In addition, bacteria are also used in the prevention of bladder cancer recurrence. In the future, urologists will need to consider possible influences of the microbiome in diagnosis and treatment of certain urological conditions. New insights might provide an opportunity to predict the risk of developing certain urological diseases and could enable the development of innovative therapeutic strategies.	bladder
Synergistic Blockade of EGFR and HER2 by New-Generation EGFR Tyrosine Kinase Inhibitor Enhances Radiation Effect in Bladder Cancer Cells.	Blockade of EGFR has been proved useful in enhancing the effect of radiotherapy, but the advantages of new-generation EGFR tyrosine kinase inhibitors (TKI) in radiosensitization are not well known. We used two human bladder cancer cells with wild-type EGFR to study the synergism between irradiation and afatinib (an EGFR/HER2 dual kinase inhibitor) or erlotinib (an EGFR kinase inhibitor). Here, we showed that afatinib has better radiosensitizing effect than erlotinib in increasing cancer cell killing, the percentage of apoptotic cells, and DNA damage. Afatinib is also superior to erlotinib in combining radiation to decrease tumor size, inhibit glucose metabolism, and enhance apoptotic proteins in vivo. Finally, erlotinib suppressed cell growth and induced more DNA damage in bladder cancer cells transfected with HER2 shRNA, but not in control vector-treated cells. In conclusion, concomitant blockade of radiation-activated EGFR and HER2 signaling by a new-generation EGFR TKI better inhibits the growth of bladder cancer cells both in vitro and in vivo. The absence of radiosensitization by EGFR inhibition alone and the greater radiosensitizing effect of EGFR inhibitor in HER2 knocked down cells suggest the synergism between HER2 and EGFR in determining radiosensitivity. The regained radiosensitizing activity of erlotinib implies that with proper HER2 inhibition, EGFR tyrosine kinase is still a potential target to enhance radiotherapy effect in these seemingly unresponsive bladder cancer cells.	bladder
Potent antitumor activity of Oct4 and hypoxia dual-regulated oncolytic adenovirus against bladder cancer.	Most solid tumors undergo hypoxia, leading to rapid cell division, metastasis and expansion of a cell population with hallmarks of cancer stem cells (CSCs). Tumor-selective replication of oncolytic adenoviruses may be hindered by oxygen deprivation in tumors. It is desirable to develop a potent oncolytic adenovirus, retaining its antitumor activity even in a hypoxic environment. We have previously generated an Oct4-dependent oncolytic adenovirus, namely Ad9OC, driven by nine copies of the Oct4 response element (ORE) for specifically killing Oct4-overexpressing bladder tumors. Here, we developed a novel Oct4 and hypoxia dual-regulated oncolytic adenovirus, designated AdLCY, driven by both hypoxia response element (HRE) and ORE. We showed that hypoxia-inducible factor (HIF)-2α and Oct4 were frequently overexpressed in hypoxic bladder cancer cells, and HIF-2α was involved in HRE-dependent and Oct4 transactivation. AdLCY exhibited higher cytolytic activities than Ad9OC against hypoxic bladder cancer cells, while sparing normal cells. AdLCY exerted potent antitumor effects in mice bearing human bladder tumor xenografts and syngeneic bladder tumors. It could target hypoxic CD44- and CD133-positive bladder tumor cells. Therefore, AdLCY may have therapeutic potential for targeting hypoxic bladder tumors and CSCs. As Oct4 is expressed in various cancers, AdLCY may be further explored as a broad-spectrum anticancer agent.	bladder
Involvement of epigenetics and EMT-related miRNA in arsenic-induced neoplastic transformation and their potential clinical use.	Exposure to toxicants leads to cumulative molecular changes that overtime increase a subject's risk of developing urothelial carcinoma. To assess the impact of arsenic exposure at a time progressive manner, we developed and characterized a cell culture model and tested a panel of miRNAs in urine samples from arsenic-exposed subjects, urothelial carcinoma patients, and controls. To prepare an in vitro model, we chronically exposed an immortalized normal human bladder cell line (HUC1) to arsenic. Growth of the HUC1 cells was increased in a time-dependent manner after arsenic treatment and cellular morphology was changed. In a soft agar assay, colonies were observed only in arsenic-treated cells, and the number of colonies gradually increased with longer periods of treatment. Similarly, invaded cells in an invasion assay were observed only in arsenic-treated cells. Withdrawal of arsenic treatment for 2.5 months did not reverse the tumorigenic properties of arsenic-treated cells. Western blot analysis demonstrated decreased PTEN and increased AKT and mTOR in arsenic-treated HUC1 cells. Levels of miR-200a, miR-200b, and miR-200c were downregulated in arsenic-exposed HUC1 cells by quantitative RT-PCR. Furthermore, in human urine, miR-200c and miR-205 were inversely associated with arsenic exposure (P = 0.005 and 0.009, respectively). Expression of miR-205 discriminated cancer cases from controls with high sensitivity and specificity (AUC = 0.845). Our study suggests that exposure to arsenic rapidly induces a multifaceted dedifferentiation program and miR-205 has potential to be used as a marker of arsenic exposure as well as a maker of early urothelial carcinoma detection.	bladder
MiR-221-induced PUMA silencing mediates immune evasion of bladder cancer cells.	Immune evasion of cancer cells is mainly due to the impaired transduction of apoptotic signals from immune cells to cancer cells, as well as inhibition of subsequent apoptosis signal cascades within the cancer cells. Over the past few decades, the research has focused more on the impaired transduction of the apoptotic signal from immune cells to cancer cells, rather than inhibition of the intracellular signaling pathways. In this study, miR‑221 inhibitor was transfected into bladder cancer cell lines 5637, J82 and T24 to repress the expression of miR‑221. As a result, the repression of miR‑221 on p53 upregulated modulator of apoptosis (PUMA) was abolished, resulting in increased expression of the pro-apoptotic Bax and reduced expression of the anti-apoptotic Bcl-2, which promotes apoptosis of bladder cancer cells. The expression of MMP-2, MMP-9 and VEGF-C were reduced, resulting in reduced invasiveness and infiltration capability of bladder cancer cells, thereby inhibiting the immune evasion of bladder cancer cells.	bladder